We report the upregulation of PN-1 mRNA levels in the brain of PrPSc inoculated hamsters before spongiform encephalopathological and clinical signs become evident. PN-1 a serine protease inhibitor belonging to the nexin family and superfamily of protease inhibitors, irreversibly inhibits certain proteases, particularly thrombin, by forming SDS-resistant complexes with their catalytic site serine. This complex formation mediates cellular binding, internalization and degradation of the protease. PN-1 is present in the normal adult brain and accumulates after lesions in both peripheral and central nervous systems sugesting roles in neural injury and repair processes. Although our study did not directly assess the role of PN-1 in the etiopathologenesis of prion diseases, its induction during the preclinical stages of the disease may suggest such a possibility.